Possible Advantage of Glucagon-Like Peptide 1 Receptor Agonists for Kidney Transplant Recipients With Type 2 Diabetes

Abstract

Context Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have the potential to improve native kidney function. Objective This work aimed to elucidate the possible protective effects of GLP-1 RAs on kidney graft function after successful kidney transplantation (KTX). Design This was a retrospective cohort study. Patients All KTRs with type 2 diabetes who were followed-up from 1 month post-transplantation for 24 months or longer as of December 31, 2020, were included. Intervention We investigated associations between the use of GLP-1 RAs and other anti-diabetic medications (non-GLP-1 RAs) and the risk of sustained estimated glomerular filtration rate (eGFR) reduction (40% reduction compared to baseline for 4 months) for KTRs with type 2 diabetes. We calculated the propensity score of initiating GLP-1 RAs compared to that of initiating non-GLP-1 RAs as a function of baseline covariates using logistic regression. The inverse probability of the treatment-weighted odds ratio was estimated to control for baseline confounding variables. Sodium-glucose cotransporter-2 inhibitor use was a competing event. Main Outcome Measure The primary outcome was sustained eGFR reduction of at least 40% from baseline for 4 months post-transplantation. Results Seventy-three patients were GLP-1 RA users and 73 were non-GLP-1 RAs users. Six patients and one patient in the non-GLP-1 RA and GLP-1 RA groups had sustained eGFR reduction. GLP-1 RA use after KTX was associated with a lower risk of sustained eGFR reduction. Conclusion GLP-1 RAs resulted in lower eGFR reduction compared with non-GLP-1 RAs and may contribute to better kidney graft survival after KTX.

Safety and efficacy of glucagon-like peptide-1 receptor agonists among kidney transplant recipients: a systematic review and meta-analysis

“…Of these, 17 studies were subsequently removed from the analysis for the following reasons: being a systematic review, meta-analysis or case report; lacking KTRs or subgroup analysis primarily focusing on KTRs; missing outcomes of interest; and duplication of the population. Thus this systematic review ultimately included nine studies with a sample size of 338 participants, including seven retrospective cohort studies without control groups [ 12 , 43–48 ] and two retrospective cohort studies with control groups [ 49 , 50 ]. The median follow-up time was 12 months [interquartile range (IQR) 6–23] with a range from 1 to 49.4 months as shown in Table 1 .…”

“…Among the 338 participants included in this systematic review, 240 individuals received GLP-1RAs and 98 individuals from two studies [ 49 , 50 ] received non-GLP-1RAs. Almost all KTRs (98.5%) had DM, with 80% having pre-existing T2DM and 18.7% experiencing PTDM.…”

“…Overall, 65% of participants were male with a mean age of 57.0 ± 10.5 years (from 331 participants across eight studies [ 12 , 43 , 44 , 46–50 ]). The mean body weight was 89.1 ± 18.8 kg (from 169 participants across seven studies [ 12 , 43–45 , 47–49 ]) and the mean BMI was 28.9 ± 6.0 kg/m 2 (from 265 participants across seven studies [ 12 , 43–45 , 47 , 48 , 50 ]). In terms of baseline blood glucose control, the baseline HbA1c was 7.3 ± 1.2% (from 260 participants across six studies [ 43–45 , 47 , 48 , 50 ]) and fasting blood glucose was 145.1 ± 55.0 mg/dl (from 79 participants across five studies [ 12 , 43–45 , 48 ]).…”

“…The mean body weight was 89.1 ± 18.8 kg (from 169 participants across seven studies [ 12 , 43–45 , 47–49 ]) and the mean BMI was 28.9 ± 6.0 kg/m 2 (from 265 participants across seven studies [ 12 , 43–45 , 47 , 48 , 50 ]). In terms of baseline blood glucose control, the baseline HbA1c was 7.3 ± 1.2% (from 260 participants across six studies [ 43–45 , 47 , 48 , 50 ]) and fasting blood glucose was 145.1 ± 55.0 mg/dl (from 79 participants across five studies [ 12 , 43–45 , 48 ]). It should be noted that only two of the included studies reported pre-existing diabetic retinopathy, affecting 65% of the 60 patients [ 43 , 46 ].…”

“…Regarding baseline kidney function, the mean serum creatinine was 1.2 ± 0.4 mg/dl (from 79 participants across five studies [ 12 , 43–45 , 48 ]), the eGFR was 50.8 ± 18.7 ml/min/1.73 m 2 (from 252 participants across six studies [ 12 , 43–45 , 47 , 50 ]) and the UPCR was 0.16 ± 0.74 g/g (from 100 participants across five studies [ 44–48 ]). Detailed information regarding immunosuppressive agents was available in six studies with 228 participants [ 12 , 44 , 45 , 47 , 48 , 50 ]. Tacrolimus was prescribed in 99% and corticosteroids in 85% of patients.…”